Pirt contributes to uterine contraction-induced pain in mice
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RESEARCH
Pirt contributes to uterine contraction‑induced pain in mice Changming Wang1, Zhongli Wang1, Yan Yang1, Chan Zhu1, Guanyi Wu1, Guang Yu1, Tunyu Jian1, Niuniu Yang1, Hao Shi1, Min Tang1, Qian He1, Lei Lan2, Qin Liu3, Yun Guan4, Xinzhong Dong5, Jinao Duan1* and Zongxiang Tang1*
Abstract Uterine contraction-induced pain (UCP) represents a common and severe form of visceral pain. Nerve fibers that innervate uterine tissue express the transient receptor potential vanilloid channel 1 (TRPV1), which has been shown to be involved in the perception of UCP. The phosphoinositide-interacting regulator of TRP (Pirt) may act as a regulatory subunit of TRPV1. The intraperitoneal injection of oxytocin into female mice after a 6-day priming treatment with estradiol benzoate induces writhing responses, which reflect the presence of UCP. Here, we first compared writhing response between Pirt+/+ and Pirt−/− mice. Second, we examined the innervation of Pirt-expressing nerves in the uterus of Pirt−/− mice by immunofluorescence and two-photon microscopy. Third, we identified the soma of dorsal root ganglion (DRG) neurons that innerve the uterus using retrograde tracing and further characterized the neurochemical properties of these DRG neurons. Finally, we compared the calcium response of capsaicin between DRG neurons from Pirt+/+ and Pirt−/− mice. We found that the writhing responses were less intensive in Pirt−/− mice than in Pirt+/+ mice. We also observed Pirt-expressing nerve fibers in the myometrium of the uterus, and that retrogradelabeled cells were small-diameter, unmyelinated, and Pirt-positive DRG neurons. Additionally, we found that the number of capsaicin-responding neurons and the magnitude of evoked calcium response were markedly reduced in DRG neurons from Pirt−/− mice. Taken together, we speculate that Pirt plays an important role in mice uterine contractioninduced pain. Keywords: Pirt, Uterine contraction-induced pain, Dorsal root ganglion, TRPV1 Background Study of uterine contraction-induced pain (UCP) that occurs during labor or menstruation (dysmenorrhea) has received little attention compared with the study of other visceral pain conditions. The uterus is innervated by afferent hypogastric nerve fibers through which any sensory information is transmitted to the central nervous system (CNS) [1]. Although the hypogastric nerve also transmits noxious mechanical and chemical stimuli, pain induced by uterus cervical distension shows similarity to the heat hyperalgesia observed in an animal models [2]. This similarity suggests a potential role of heat-sensing *Correspondence: [email protected]; [email protected] 1 College of Basic Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Rd, Nanjing 210023, Jiangsu, China Full list of author information is available at the end of the article
ion channels in pain induced by cervical and uterine contraction. Indeed, the transient receptor potential vanilloid 1 (TRPV1), which is important to the detection of noxious heat, may contrib
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